New research presented at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer has revealed that the combination of durvalumab (Imfinzi) and chemoradiotherapy does not improve survival rates in patients with unresectable stage III non-small cell lung cancer (NSCLC). The findings, derived from the phase 3 EA5181 trial (NCT04092283), indicate that the concurrent administration of durvalumab does not provide a survival advantage compared to chemoradiotherapy alone, followed by consolidation durvalumab.
In the trial, the median overall survival (OS) for patients receiving concurrent durvalumab was reported at 41.5 months (95% CI, 34.4-not reached) compared to 39.4 months (95% CI, 33.4-not reached) for those treated with chemoradiotherapy alone. The hazard ratio was calculated at 1.03 (95% CI, 0.80-1.32; P = .83), showing no significant difference in survival outcomes. Similarly, the median progression-free survival (PFS) was 15.5 months in the durvalumab group versus 16.4 months in the chemoradiation arm (HR, 1.05; 95% CI, 0.86-1.29; P = .65).
Dr. John M. Varlotto, professor and chief of Radiation Oncology at Marshall Health, emphasized during the presentation that the addition of durvalumab during chemotherapy and radiation did not enhance OS or PFS, nor did it alter recurrence patterns or overall response rates (ORRs). “The results indicate that this treatment strategy did not increase toxicity,” he noted.
The trial enrolled a total of 662 patients, who were randomly assigned in a 1:1 ratio to receive either durvalumab combined with platinum doublet chemotherapy and three concurrent rounds of radiotherapy at 60 Gy, or platinum doublet chemotherapy with radiotherapy alone, also at 60 Gy. Following the chemoradiation phase, patients had the option to transition to consolidation durvalumab at 1500 mg every four weeks for one year.
Patients included in the trial had to meet specific criteria, including a diagnosis of unresectable stage IIIA to C NSCLC and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. The primary endpoint of the study was OS, with secondary endpoints focusing on PFS, toxicity, ORRs, and recurrence patterns.
The demographic breakdown showed that approximately 60.6% of participants were male, with a median age of 67.1 years (range, 37.6-89.4). Within the cohort, 50.6% had stage IIIA disease, and 48.7% were diagnosed with adenocarcinoma. Notably, 53.3% of patients were former smokers, and 82.5% received a regimen of carboplatin and paclitaxel.
Disease progression was observed in 45.4% of patients in the durvalumab group and 44.0% in the chemoradiation arm. Local recurrence rates were 55.9% and 49.6% (P = .34), respectively, while in-field radiation recurrences were similarly low at 28.6% and 28.4% (P = .98).
The overall response rate before consolidation was 51.3% in the durvalumab arm compared to 47.1% in the chemoradiation-only group (P = .28). During the consolidation phase, ORRs were 71.5% and 67.1% (P = .31), indicating comparable effectiveness.
Adverse effects (AEs) were prevalent across both treatment arms, with any grade of AEs reported in 99.1% of patients receiving durvalumab versus 98.7% in the chemoradiation group. Grade 3 or 4 AEs occurred in 67.7% of the durvalumab cohort compared to 62.2% in the chemoradiation group. Serious AEs were noted in 3.6% of patients in the durvalumab arm versus 3.5% in the other arm, while AEs leading to treatment discontinuation affected 19.0% versus 16.5% of patients, respectively.
The most frequently observed grade 3 to 5 treatment-related AEs included a decrease in lymphocyte count (50% vs. 45%), white blood cell count decrease (22% vs. 27%), and esophagitis (21% vs. 27%), among others.
The study, which had a median follow-up period of 29.9 months (95% CI, 28.4-33.1), highlighted that while durvalumab is a promising therapy, its concurrent administration with chemoradiotherapy may not provide the anticipated benefits for patients suffering from advanced-stage lung cancer.
This research adds to the growing body of evidence guiding treatment strategies for lung cancer and underscores the need for continued exploration of effective therapies for this challenging disease.